The long term goal of this research program is to understand how eukaryotic DNA replication is regulated during the cell cycle. This question is central to understanding the mechanisms that control cellular proliferation in normal cells, as well as the perturbations of normal growth control that result in cancer. We have chosen Schizosaccharomyces pombe as an experimental system because it has many similarities to higher eukaryotic cells and because it has already proved to be a powerful tool for probing cell cycle control. Our approach to problem of how DNA replication is regulated in S. pombe is twofold. First, we plan to use genetic and biochemical methods to identify and characterize genes that couple the basic cell cycle engine to the initiation of DNA replication. Second we will analyze the structure and function of the S pombe origin of replication, ARS1, with the aim of identifying and characterizing interacting proteins involved in initiation. We expect that information obtained in our studies will complement that obtained from the study of S. cerevisae and will be directly relevant to the control of DNA replication in higher eukaryotes.